We propose to analyze idiotype-specific cellular interactions using Balb/c myeloma cells, hybridoma cells and their idiotypic markers as a model system. Idiotype-specific interactions will be studied both from the effector cell aspect analyzing the induction of functional interaction of different subsets of lymphocytes expressing complementary idiotypes, as well a from the target cell aspect evaluating how quantitative changes in surface antigen expression affect the susceptibility of the myeloma cells to anti-idiotypic regulation. In studying the induction and functional interaction of cells expressing complementary idiotypes, populations of T and B cells will be purified with respect to specific surface markers and idiotypic or anti-idiotypic determinants using the Fluorescence Activated Cell Sorter. We will then determine how these subsets of lymphocytes bearing idiotypic and anti-idiotypic receptors regulate each other and how they affect the proliferation and function of idiotype-bearing myeloma cells and anti-idiotype-bearing hybridoma cells. Assays which can detect stimulatory, cytostatic, or cytolytic effects will be used to explore the mechanisms and restrictions which allow meaningful positive and negative regulatory network interactions between different clones of complementary lymphocytes. In studying the role of quantitative changes in surface antigen expression on the susceptibility of target cells to idiotype-specific immune regulation, we will evaluate how both heritable variants and nonheritable changes in surface idiotype and H-2 expression are generated and assess the importance of quantitative changes in antigen expression on the susceptibility of these cells to idiotype-specific immune regulation. Nonheritable changes in susceptibility of myeloma cells to anti-idiotypic immunity, are observed in vitro after drug treatment. We will test in vivo if similar non-heritable changes in sensitivity to regulation can be observed.